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Updated: Feb 28, 2026
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Effect of cisplatin on the transport activity of PII-type ATPases
Francesco Tadini-Buoninsegni1, Giacomo Sordi, Serena Smeazzetto
1Department of Chemistry "Ugo Schiff", University of Florence, 50019 Sesto Fiorentino, Italy. francesco.tadini@unifi.it.
Abstract:
Cisplatin (cis-diamminedichlorido-Pt(ii)) is extensively used as a chemotherapeutic agent against various types of tumors. However, cisplatin administration causes serious side effects, including nephrotoxicity, ototoxicity and neurotoxicity. It has been shown that cisplatin can interact with P-type ATPases, e.g., Cu+-ATPases (ATP7A and ATP7B) and Na+,K+-ATPase. Cisplatin-induced inhibition of Na+,K+-ATPase has been related to the nephrotoxic effect of the drug. To investigate the inhibitory effects of cisplatin on the pumping activity of PII-type ATPases, electrical measurements were performed on sarcoplasmic reticulum Ca2+-ATPase (SERCA) and Na+,K+-ATPase embedded in vesicles/membrane fragments adsorbed on a solid-supported membrane. We found that cisplatin inhibits SERCA and Na+,K+-ATPase only when administered without a physiological reducing agent (GSH); in contrast, inhibition was also observed in the case of Cu+-ATPases in the presence of 1 mM GSH. Our results indicate that cisplatin is a much stronger inhibitor of SERCA (with an IC50 value of 1.3 μM) than of Na+,K+-ATPase (with an IC50 value of 11.1 μM); moreover, cisplatin inhibition of Na+,K+-ATPase is reversible, whereas it is irreversible in the case of SERCA. In the absence of a physiological substrate, while Cu+-ATPases are able to translocate cisplatin, SERCA and Na+,K+-ATPase do not perform ATP-dependent cisplatin displacement.
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